There are various types of samples in the field of analytical chemistry, and particularly in the medical field, body fluids such as blood, urine, spinal fluid, saliva, and the like, are important subjects for analysis. A need has arisen for analyzing such samples in large amounts and collectively.
In order to meet this need, a sample analysis device, having a reagent film previously impregnated with a reagent and stuck on a strip, has been developed and used. In such a device, the reagent film is supplied with a sample such as blood, and the sample is allowed to react with the reagent to generate a pigment, which develops a color in the reagent film, and then the degree of the color is analyzed by an optical measuring apparatus such as a densitometer. By using this device, operations for preparing a reagent and allowing the reagent to react with the sample can be simplified, so that the whole analysis operation can be converted into a routine exercise.
In such a sample analysis device, examples of methods for supplying the reagent film with a sample include a method utilizing capillarity, spotting, dipping, and the like. Among these methods, methods utilizing capillarity have been most commonly used. Because it is required to intercept external light during optical measuring, the sample supplying portion and the analysis section must be positioned at a considerable distance from one another when the device is set in an optical measuring apparatus. Therefore, the sample must be moved in the device, capillarity being used as the means for moving the sample. Examples of devices utilizing capillarity are disclosed in Japanese Published Unexamined Patent Application No. Hei 4-188065 and Japanese Published Unexamined Patent Application No. Sho 57-132900.
FIG. 10 shows one example of a sample analysis device utilizing capillarity. As shown in the drawing, the device has a triangular shaped sampling point 42 protruding from an approximately center portion of the front face 44 of a transparent base member 47 made of acrylic resin, a groove 46 extending from the sampling point 42 toward the back portion of the base member 47, and a slot 45 formed as an extension of the groove. Furthermore, a reagent film 48 is stuck on the upper face of the base member 47 on the side of the front face 44 so that it may cover the groove 46. The structure of the reagent film 48 is determined as appropriate depending on the type of the sample. For example, when analyzing plasma components of blood, the reagent film used comprises a filtration layer, a reagent layer, a transparent protective layer, and an opaque protective layer, which are laminated in this order from the bottom, and in which an observation window 50 for entering light is formed in an approximately center portion in the opaque protective layer.
Analysis using this device may be carried out as in the following steps. First, a drop of blood is obtained from a subject and brought into contact with the sampling point 42. Then, the blood is drawn into the groove 46 by capillarity and the whole groove is filled with the blood. When the blood permeates into the reagent film 48 covering the upper portion of the groove 46, first erythrocytes are removed by the filtration layer, and plasma components reach the reagent layer and are allowed to react with the reagent to generate a pigment, which develops a color in the reagent layer. In this state, the device is set in an optical measuring apparatus such as a densitometer, where the degree of the color developed in the reagent layer is measured by irradiating light through the observation window 50.
However, in using a device utilizing capillarity, there are problems as described below.
First, because a capillary channel needs to be continuously filled with a sample in order to cause capillarity, the sample must be provided in a larger amount than is required in analysis. In addition, because it takes some time to introduce the sample by capillarity, measuring cannot be carried out quickly. Furthermore, in body fluids such as blood, there are individual differences in properties such as viscosity, which affect capillarity, so that time required for introducing the sample into the analysis section or the like cannot be fixed. As a result, the time required for analysis, including the time for reaction with a reagent, is difficult to be fixed, and also an error might be caused in the analysis results. Furthermore, since the drawing force by capillarity is very weak, it is easily affected by gravity. Therefore, when introducing a sample, the inclination of the device has to be restricted, and also the structure of the optical measuring apparatus used is limited. Furthermore, the sample supplying portion and the analysis section cannot be positioned at a distance from each other because of the weakness of the drawing force by capillarity, therefore, in an optical measuring apparatus, possibilities of contamination of the measuring apparatus during introduction of a sample, or influence of external light, cannot be completely eliminated.
On the other hand, the spotting method for supplying samples has the disadvantage in that, when using blood as the sample, the sampling spot is limited to a fingertip, and sampling from an ear or the abdomen is difficult to perform.